Toll-like receptor 9–dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE
Abstract
Increased concentrations of DNA-containing immune complexes in the serum are associated with systemic autoimmune diseases such as lupus. Stimulation of Toll-like receptor 9 (TLR9) by DNA is important in the activation of plasmacytoid dendritic cells and B cells. Here we show that HMGB1, a nuclear DNA-binding protein released from necrotic cells, was an essential component of DNA-containing immune complexes that stimulated cytokine production through a TLR9-MyD88 pathway involving the multivalent receptor RAGE. Moreover, binding of HMGB1 to class A CpG oligodeoxynucleotides considerably augmented cytokine production by means of TLR9 and RAGE. Our data demonstrate a mechanism by which HMGB1 and RAGE activate plasmacytoid dendritic cells and B cells in response to DNA and contribute to autoimmune pathogenesis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Neutralization of Mincle inhibits neutrophil recruitment and pro-inflammatory cytokine production after intraperitoneal injection of dead tumor cells, indicating a role for SAP130-Mincle in immunogenicity of dead cells in vivo.
“Neutralization of Mincle with a specific antibody inhibited the recruitment of neutrophils and pro-inflammatory cytokine production following intraperitoneal injection of dead tumor cells54, indicating a role for SAP130–Mincle in the immunogenicity of dead cells in vivo.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [54]
SAP130 is released by necrotic and late apoptotic cells and binds Mincle, an ITAM-coupled activating receptor mainly expressed by macrophages.
“A recent study has identified spliceosome-associated protein 130 (SAP130), which is a component of small nuclear ribonucleoprotein, as another DAMP that is released by necrotic and late apoptotic cells 54. SAP130 specifically binds to macrophage-inducible C-type lectin (Mincle/Clec4e), which is an immunoreceptor tyrosine-based activation motif (ITAM)-coupled activating receptor that is mainly”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [54]
The HMGB1-bound DNA complex with TLR9 and RAGE may be important for promoting inflammation in patients with systemic lupus erythematosus who have elevated circulating levels of DNA-containing immune complexes.
“Specifically, HMGb1-bound DNA can form a complex with TLR9 and RAGe to induce pro-inflammatory cytokines98, which may be important for promoting inflammation in patients with systemic lupus erythematosus who have elevated circulating levels of DNA-containing immune complexes.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [98]
In certain cases, RAGE may transduce signals by acting cooperatively with TLRs.
“In certain cases, RAGe may transduce signals by acting cooperatively with TLRs.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [98]
HMGB1-bound DNA can form a complex with TLR9 and RAGE to induce pro-inflammatory cytokines.
“Specifically, HMGb1-bound DNA can form a complex with TLR9 and RAGe to induce pro-inflammatory cytokines98, which may be important for promoting inflammation in patients with systemic lupus erythematosus who have elevated circulating levels of DNA-containing immune complexes.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [98]
Cites
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221 · see citing works
HMG-1 as a Late Mediator of Endotoxin Lethality in Mice
Wang, H., Bloom, O., Zhang, M., Vishnubhakat, J. M., Ombrellino, M., Che, J., Frazier, A., Yang, H., Ivanova, S., Borovikova, L. V., et al. (1999) · Science · doi:10.1126/science.285.5425.248 · Cited by 3,386 · see citing works
Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood
Bennett, L. B., Palucka, K., Arce, E., Cantrell, V., Borvák, J., Banchereau, J., & Pascual, V. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021553 · Cited by 1,962 · see citing works
Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors
Leadbetter, E. A., Rifkin, I. R., Hohlbaum, A. M., Beaudette-Zlatanova, B. C., Shlomchik, M. J., & Marshak‐Rothstein, A. (2002) · Nature · doi:10.1038/416603a · Cited by 1,899 · see citing works
Self-citationHuman TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition
Bauer, S., Kirschning, C. J., Häcker, H., Redecke, V., Hausmann, S., Akira, S., Wagner, H., & Lipford, G. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161293498 · Cited by 1,527 · see citing works
Andersson, U., Wang, H., Palmblad, K., Aveberger, A.-C., Bloom, O., Erlandsson-Harris, H., Janson, A., Kokkola, R., Zhang, M., Yang, H., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.4.565 · Cited by 1,401 · see citing works
TLR9 signals after translocating from the ER to CpG DNA in the lysosome
Latz, E., Schoenemeyer, A., Visintin, A., Fitzgerald, K. A., Monks, B. G., Knetter, C. F., Lien, E., Nilsen, N. J., Espevik, T., & Golenbock, D. T. (2004) · Nature Immunology · doi:10.1038/ni1028 · Cited by 1,355 · see citing works
Self-citationInduction of Dendritic Cell Differentiation by IFN-α in Systemic Lupus Erythematosus
Blanco, P., Palucka, A. K., Gill, M. A., Pascual, V., & Banchereau, J. (2001) · Science · doi:10.1126/science.1064890 · Cited by 1,265 · see citing works
Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
Bonaldi, T., Talamo, F., Scaffidi, P., Ferrera, D., Porto, A., Bachi, A., Rubartelli, A., Agresti, A., & Bianchi, M. E. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg516 · Cited by 1,252 · see citing works
Therapeutic potential of Toll-like receptor 9 activation
Krieg, A. Μ. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2059 · Cited by 1,244 · see citing works
Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases
Taguchi, A., Blood, D. C., del Toro, G., Canet, A., Lee, D. C., Qu, W., Tanji, N., Lu, Y., Lalla, E., Fu, C., et al. (2000) · Nature · doi:10.1038/35012626 · Cited by 1,217 · see citing works
Napolitani, G., Rinaldi, A., Bertoni, F., Sallusto, F., & Lanzavecchia, A. (2005) · Nature Immunology · doi:10.1038/ni1223 · Cited by 1,156 · see citing works
The Receptor for Advanced Glycation End Products (RAGE) Is a Cellular Binding Site for Amphoterin
Hori, O., Brett, J., Slattery, T., Cao, R., Zhang, J., Chen, J. X., Nagashima, M., Lundh, E. R., Vijay, S., Nitecki, D., et al. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.43.25752 · Cited by 1,151 · see citing works
Reversing established sepsis with antagonists of endogenous high-mobility group box 1
Yang, H., Ochani, M., Li, J., Qiang, X., Tanovic, M., Harris, H. E., Susarla, S. M., Ulloa, L., Wang, H., DiRaimo, R., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2434651100 · Cited by 1,126 · see citing works
Jego, G., Palucka, A. K., Blanck, J.-P., Chalouni, C., Pascual, V., & Banchereau, J. (2003) · Immunity · doi:10.1016/s1074-7613(03)00208-5 · Cited by 1,067 · see citing works
Pathogenesis of systemic lupus erythematosus
Mok, C. C., & Lau, C. S. (2003) · Journal of Clinical Pathology · doi:10.1136/jcp.56.7.481 · Cited by 947 · see citing works
High mobility group box 1 protein interacts with multiple Toll-like receptors
Park, J. S., Gamboni-Robertson, F., He, Q., Svetkauskaite, D., Kim, J., Strassheim, D., Sohn, J.-W., Yamada, S., Maruyama, I., Banerjee, A. M., et al. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00401.2005 · Cited by 934 · see citing works
Barrat, F. J., Meeker, T., Gregorio, J. D., Chan, J. H., Uematsu, S., Akira, S., Chang, B., Duramad, O., & Coffman, R. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050914 · Cited by 932 · see citing works
Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells
Fiuza, C., Bustin, M., Talwar, S., Tropea, M., Gerstenberger, E. P., Shelhamer, J. H., & Suffredini, A. F. (2003) · Blood · doi:10.1182/blood-2002-05-1300 · Cited by 737 · see citing works
Kirou, K. A., Lee, C., George, S., Louca, K., Peterson, M. G. E., & Crow, M. K. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21031 · Cited by 702 · see citing works
Self-citationBarton, G. M., Kagan, J. C., & Medzhitov, R. M. (2005) · Nature Immunology · doi:10.1038/ni1280 · Cited by 669 · see citing works
Gottenberg, J., Cagnard, N., Lucchesi, C., Letourneur, F., Mistou, S., Lazure, T., Jacques, S., Bâ, N., Ittah, M., Lepajolec, C., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510837103 · Cited by 606 · see citing works
The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins
Chavakis, T., Bierhaus, A., Al‐Fakhri, N., Schneider, D., Witte, S., Linn, T., Nagashima, M., Morser, J., Arnold, B., Preissner, K. T., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030800 · Cited by 583 · see citing works
Self-citationTer Borg, E. J., Horst, G., Hummel, E. J., Limburg, P. C., & Kallenberg, C. G. M. (1990) · Arthritis & Rheumatism · doi:10.1002/art.1780330505 · Cited by 572 · see citing works
Lövgren, T., Eloranta, M., Båve, U., Alm, G. V., & Rönnblom, L. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20254 · Cited by 553 · see citing works
Activation of Autoreactive B Cells by CpG dsDNA
Viglianti, G. A., Lau, C. M., Hanley, T. M., Miko, B. A., Shlomchik, M. J., & Marshak‐Rothstein, A. (2003) · Immunity · doi:10.1016/s1074-7613(03)00323-6 · Cited by 519 · see citing works
Self-citationDumitriu, I. E., Baruah, P., Valentinis, B., Voll, R. E., Herrmann, M., Nawroth, P. P., Arnold, B., Bianchi, M. E., Manfredi, A. A., & Rovere-Querini, P. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.12.7506 · Cited by 503 · see citing works
RAGE is the Major Receptor for the Proinflammatory Activity of HMGB1 in Rodent Macrophages
Kokkola, R., Andersson, Å., Mullins, G. E., Östberg, T., Treutiger, C.-J., Arnold, B., Nawroth, P. P., Andersson, J., Harris, R. A., & Harris, H. E. (2005) · Scandinavian Journal of Immunology · doi:10.1111/j.0300-9475.2005.01534.x · Cited by 496 · see citing works
Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation
Palumbo, R., Sampaolesi, M., Marchis, F. D., Tonlorenzi, R., Colombetti, S., Mondino, A., Cossu, G., & Bianchi, M. E. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200304135 · Cited by 469 · see citing works
Degryse, B., Bonaldi, T., Scaffidi, P., Müller, S., Resnati, M., Sanvito, F., Arrigoni, G., & Bianchi, M. E. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.6.1197 · Cited by 451 · see citing works
Extracellular role of HMGB1 in inflammation and sepsis
Wang, H., Yang, H., & Tracey, K. J. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2003.01302.x · Cited by 439 · see citing works
The double life of HMGB1 chromatin protein: architectural factor and extracellular signal
Müller, S., Scaffidi, P., Degryse, B., Bonaldi, T., Ronfani, L., Agresti, A., Beltrame, M., & Bianchi, M. E. (2001) · The EMBO Journal · doi:10.1093/emboj/20.16.4337 · Cited by 427 · see citing works
Role of HMGB1 in apoptosis-mediated sepsis lethality
Qin, S., Wang, H., Yuan, R., Li, H., Ochani, M., Ochani, K., Rosas‐Ballina, M., Czura, C. J., Huston, J. M., Miller, E., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052203 · Cited by 401 · see citing works
Self-citationGuiducci, C., Ott, G. S., Chan, J. H., Damon, E., Calacsan, C., Matray, T. J., Lee, K., Coffman, R. L., & Barrat, F. J. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060401 · Cited by 391 · see citing works
Ehlers, M., Fukuyama, H., McGaha, T. L., Aderem, A. A., & Ravetch, J. V. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052438 · Cited by 338 · see citing works
Sappington, P. L., Yang, R., Yang, H., Tracey, K. J., Delude, R. L., & Fink, M. P. (2002) · Gastroenterology · doi:10.1053/gast.2002.35391 · Cited by 319 · see citing works
Hua, J., Kirou, K. A., Lee, C. L. L., & Crow, M. K. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21890 · Cited by 317 · see citing works
Self-citationProduction of type I interferons
Asselin‐Paturel, C., & Trinchieri, G. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051395 · Cited by 304 · see citing works
High mobility group box chromosomal protein 1: A novel proinflammatory mediator in synovitis
Kokkola, R., Sundberg, E., Ulfgren, A. ‐., Palmblad, K., Li, J., Wang, H., Ulloa, L., Yang, H., Yan, X. ‐., Furie, R., et al. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10540 · Cited by 290 · see citing works
Vallin, H., Perers, A., ALM, G. V., & Rönnblom, L. (1999) · PubMed · Cited by 284 · see citing works
Vallin, H., Perers, A., Alm, G. V., & Rönnblom, L. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.11.6306 · Cited by 256 · see citing works
Innate immune recognition of, and regulation by, DNA
Ishii, K. J., & Akira, S. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.09.002 · Cited by 222 · see citing works
Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells
Dumitriu, I. E., Baruah, P., Bianchi, M. E., Manfredi, A. A., & Rovere, P. Q. (2005) · European Journal of Immunology · doi:10.1002/eji.200526066 · Cited by 203 · see citing works
Ishihara, K., Tsutsumi, K., Kawane, S., Nakajima, M., & Kasaoka, T. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00846-9 · Cited by 201 · see citing works
HMGB1 is a potent trigger of arthritis
Andersson, J., & Erlandsson-Harris, H. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2003.01303.x · Cited by 169 · see citing works
On Spectral Relaxation in Proteins†¶‖
Lakowicz, J. R. (2000) · Photochemistry and Photobiology · doi:10.1562/0031-8655(2000)0720421osrip2.0.co2 · Cited by 155 · see citing works
Recombinant HMGB1 with cytokine-stimulating activity.
Li, J.-H., Wang, H., Mason, J. M., Levine, J., Yu, M., Ulloa, L., Czura, C., Tracey, K., & Yang, H. (2004) · JIM - Journal of Immunological Methods · doi:10.1016/j.jim.2004.04.019 · Cited by 142 · see citing works
Popovic, K., Ek, M., Espinosa, A., Padyukov, L., Harris, H. E., Wahren‐Herlenius, M., & Nyberg, F. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21398 · Cited by 140 · see citing works
Role of Natural Interferon-α Producing Cells (Plasmacytoid Dendritic Cells) in Autoimmunity
Rönnblom, L., Eloranta, M., & Alm, G. V. (2003) · Autoimmunity · doi:10.1080/08916930310001602128 · Cited by 137 · see citing works
Structure of a Complex of Tandem HMG Boxes and DNA
Stott, K. M., Tang, G. S. F., Lee, K., & Thomas, J. O. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.04.059 · Cited by 130 · see citing works
Denny, M. F., Chandaroy, P., Killen, P. D., Caricchio, R., Lewis, E. E., Richardson, B. C., Lee, K.-D., Gavalchin, J., & Kaplan, M. J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.4.2095 · Cited by 128 · see citing works
Sorci, G., Riuzzi, F., Arcuri, C., Giambanco, I., & Donato, R. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.11.4880-4894.2004 · Cited by 125 · see citing works
Natural Interferon-α Producing Cells: The Plasmacytoid Dendritic Cells
Fitzgerald-Bocarsly, P. A. (2002) · BioTechniques · doi:10.2144/oct0203 · Cited by 119 · see citing works
Antagonism of RAGE suppresses peripheral nerve regeneration
Rong, L., Trojaborg, W., Qu, W., Kostov, K., Yan, S. D., Gooch, C. L., Szabolcs, M. J., Hays, A. P., & Schmidt, A. M. (2004) · The FASEB Journal · doi:10.1096/fj.04-1899com · Cited by 113 · see citing works
Langenkamp, A., Casorati, G., Garavaglia, C., Dellabona, P., Lanzavecchia, A., & Sallusto, F. (2002) · European Journal of Immunology · doi:10.1002/1521-4141(200207)32:7 · Cited by 113 · see citing works
Necessity of Oligonucleotide Aggregation for Toll-like Receptor 9 Activation
Wu, C. C. N., Lee, J., Raz, E., Corr, M., & Carson, D. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311662200 · Cited by 83 · see citing works
Magnusson, M., Magnusson, S., Vallin, H., Rönnblom, L., & Alm, G. V. (2001) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2001.01018.x · Cited by 74 · see citing works
Popovič, P., DeMarco, R., Lotze, M. T., Winikoff, S. E., Bartlett, D. L., Krieg, A. Μ., Guo, Z. S., Brown, C. K., Tracey, K. J., & Zeh, H. J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.12.8701 · Cited by 68 · see citing works
Binding Properties of Human Anti‐DNA Antibodies to Cloned Human DNA Fragments
Sano, H., TAKAI, O., Harata, N. C., YOSHINAGA, K., KODAMA‐KAMADA, I., & Sasaki, T. (1989) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.1989.tb01188.x · Cited by 65 · see citing works
Toll‐Like Receptor Activation in the Pathogenesis of Systemic Lupus Erythematosus
Means, T. K., & Luster, A. D. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1358.027 · Cited by 61 · see citing works
Interferon pathway activation in systemic lupus erythematosus
Crow, M. K. (2005) · Current Rheumatology Reports · doi:10.1007/s11926-005-0053-4 · Cited by 43 · see citing works
Self-citationMarshak‐Rothstein, A., Busconi, L., Lau, C. M., Tabor, A. S., Leadbetter, E. A., Akira, S., Krieg, A. Μ., Lipford, G. B., Viglianti, G. A., & Rifkin, I. R. (2004) · Journal of Endotoxin Research · doi:10.1179/096805104225005850 · Cited by 38 · see citing works
Self-citationA COMPARISON OF THE AMINO‐TERMINAL SEQUENCES OF TWO CALF‐THYMUS CHROMATIN NON‐HISTONE PROTEINS
Walker, J. M., Goodwin, G. H., Johns, E. W., et al. (1977) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1977.tb03484.x · Cited by 27 · see citing works
Discriminating Microbe from Self Suffers a Double Toll
Goodnow, C. C. (2006) · Science · doi:10.1126/science.1129797 · Cited by 25 · see citing works
Robak, E., Sysa‐Jędrzejowska, A., Robak, T., et al. (2006) · Clinical Rheumatology · doi:10.1007/s10067-005-1163-0 · Cited by 25 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895 · see citing works
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · see citing works
Mechanisms of Diabetic Complications
Forbes, J. M., & Cooper, M. E. (2013) · Physiological Reviews · doi:10.1152/physrev.00045.2011 · Cited by 2,890 · see citing works
Toll-like Receptors and the Control of Immunity
Fitzgerald, K. A., & Kagan, J. C. (2020) · Cell · doi:10.1016/j.cell.2020.02.041 · Cited by 2,168 · see citing works
Self-citationDAMP-sensing receptors in sterile inflammation and inflammatory diseases
Gong, T., Liu, L., Jiang, W., & Zhou, R. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0215-7 · Cited by 1,672 · see citing works
HMGB1 is a therapeutic target for sterile inflammation and infection
Andersson, U., & Tracey, K. J. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101323 · Cited by 1,437 · see citing works
Immunogenic and tolerogenic cell death
Green, D. R., Ferguson, T., Zitvogel, L., & Kroemer, G. (2009) · Nature Reviews Immunology · doi:10.1038/nri2545 · Cited by 1,176 · see citing works
Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases
Gilliet, M., Cao, W., & Liu, Y.-J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2358 · Cited by 1,190 · see citing works
Role of advanced glycation end products in cellular signaling
Ott, C., Jacobs, K., Haucke, E., Navarrete Santos, A., Grune, T., & Simm, A. (2014) · Redox Biology · doi:10.1016/j.redox.2013.12.016 · Cited by 1,150 · see citing works
Phagocyte partnership during the onset and resolution of inflammation
Soehnlein, O., & Lindbom, L. (2010) · Nature Reviews Immunology · doi:10.1038/nri2779 · Cited by 1,054 · see citing works
Decoding cell death signals in liver inflammation
Brenner, C., Galluzzi, L., Kepp, O., & Kroemer, G. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.033 · Cited by 1,022 · see citing works
Kang, R., Chen, R., Zhang, Q., Hou, W., Wu, S., Cao, L., Huang, J., Yu, Y., Fan, X.-G., Yan, Z., et al. (2014) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.05.001 · Cited by 956 · see citing works
Chiba, S., Baghdadi, M., Akiba, H., Yoshiyama, H., Kinoshita, I., Dosaka-Akita, H., Fujioka, Y., Ohba, Y., Gorman, J. V., Colgan, J. D., et al. (2012) · Nature Immunology · doi:10.1038/ni.2376 · Cited by 838 · see citing works
CD24 and Siglec-10 Selectively Repress Tissue Damage–Induced Immune Responses
Chen, G.-Y., Tang, J., Zheng, P., & Liu, Y. (2009) · Science · doi:10.1126/science.1168988 · Cited by 786 · see citing works
HMGB1: Endogenous Danger Signaling
Klune, J. R., Dhupar, R., Cardinal, J., Billiar, T. R., & Tsung, A. (2008) · Molecular Medicine · doi:10.2119/2008-00034.klune · Cited by 762 · see citing works
Tohme, S., Yazdani, H. O., Al-Khafaji, A. B., Chidi, A. P., Loughran, P., Mowen, K., Wang, Y., Simmons, R. L., Huang, H., & Tsung, A. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-1591 · Cited by 694 · see citing works
HMGB1: A multifunctional alarmin driving autoimmune and inflammatory disease
Harris, H. E., Andersson, U., & Pisetsky, D. S. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.222 · Cited by 689 · see citing works
Self‐assembled DNA nanoclews for the efficient delivery of CRISPR–Cas9 for genome editing
Sun, W., Ji, W., Hall, J. M., Hu, Q., Wang, C., Beisel, C. L., & Gu, Z. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201506030 · Cited by 629 · see citing works
Kazama, H., Ricci, J.-E., Herndon, J. M., Hoppe, G., Green, D. R., & Ferguson, T. A. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.013 · Cited by 627 · see citing works
High‐mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity
Bianchi, M. E., & Manfredi, A. A. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00574.x · Cited by 600 · see citing works
Nucleic acid recognition by the innate immune system
Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577 · see citing works
Linking oxidative stress to inflammation: Toll-like receptors
Gill, R., Tsung, A., & Billiar, T. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.01.006 · Cited by 553 · see citing works
Yang, H., Antoine, D. J., Andersson, U., & Tracey, K. J. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.1212662 · Cited by 542 · see citing works
HMGB1 release and redox regulates autophagy and apoptosis in cancer cells
Tang, D., Kang, R., Cheh, C.-W., Livesey, K. M., Liang, X., Schapiro, N. E., Benschop, R., Sparvero, L. J., Amoscato, A. A., Tracey, K. J., et al. (2010) · Oncogene · doi:10.1038/onc.2010.261 · Cited by 461 · see citing works
p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes
Davalos, A. R., Kawahara, M., Malhotra, G. K., Schaum, N., Huang, J., Ved, U., Beausejour, C. M., Coppe, J.-P., Rodier, F., & Campisi, J. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201206006 · Cited by 439 · see citing works
HMGB1, IL-1α, IL-33 and S100 proteins: dual-function alarmins
Bertheloot, D., & Latz, E. (2017) · Cellular & Molecular Immunology · doi:10.1038/cmi.2016.34 · Cited by 455 · see citing works
Self-citationTaming lupus-a new understanding of pathogenesis is leading to clinical advances
Liu, Z., & Davidson, A. (2012) · Nature Medicine · doi:10.1038/nm.2752 · Cited by 433 · see citing works
Uric Acid Is a Danger Signal Activating NALP3 Inflammasome in Lung Injury Inflammation and Fibrosis
Gasse, P., Riteau, N., Charron, S., Girre, S., Fick, L., Pétrilli, V., Tschopp, J., Lagente, V., Quesniaux, V. F. J., Ryffel, B., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200808-1274oc · Cited by 410 · see citing works
Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons
Gregorio, J., Meller, S., Conrad, C., Di Nardo, A., Homey, B., Lauerma, A., Arai, N., Gallo, R. L., DiGiovanni, J., & Gilliet, M. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20101102 · Cited by 367 · see citing works
Microglia: Agents of the CNS Pro-Inflammatory Response
Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020) · Cells · doi:10.3390/cells9071717 · Cited by 365 · see citing works
High-mobility group box 1 protein (HMGB1) operates as an alarmin outside as well as inside cells
Andersson, U., Yang, H., & Harris, H. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.02.011 · Cited by 309 · see citing works
Cell-Free DNA as a Biomarker in Autoimmune Rheumatic Diseases
Duvvuri, B., & Lood, C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00502 · Cited by 282 · see citing works
DAMPs as mediators of sterile inflammation in aging-related pathologies
Feldman, N., Rotter-Maskowitz, A., & Okun, E. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.01.003 · Cited by 283 · see citing works
Danger-associated molecular patterns in Alzheimer’s disease
Venegas, C., & Heneka, M. T. (2017) · Journal of Leukocyte Biology · doi:10.1189/jlb.3mr0416-204r · Cited by 236 · see citing works
HMGB1 in Development and Diseases of the Central Nervous System
Fang, P., Schachner, M., & Shen, Y.-Q. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8264-y · Cited by 193 · see citing works
High‐mobility group box‐1 in sterile inflammation
Tsung, A., Tohme, S., & Billiar, T. R. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12276 · Cited by 187 · see citing works
Ryu, C., Sun, H., Gulati, M., Herazo-Maya, J. D., Chen, Y., Osafo-Addo, A., Brandsdorfer, C., Winkler, J., Blaul, C., Faunce, J., et al. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201612-2480oc · Cited by 171 · see citing works
Pattern recognition receptors in the immune response against dying cells
Jeannin, P., Jaillon, S., & Delneste, Y. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2008.04.013 · Cited by 165 · see citing works
Prognostic and predictive value of DAMPs and DAMP-associated processes in cancer
Fucikova, J., Moserova, I., Urbanova, L., Bezu, L., Kepp, O., Cremer, I., Salek, C., Strnad, P., Kroemer, G., Galluzzi, L., et al. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00402 · Cited by 159 · see citing works
Toll-like Receptor 4 and Hepatic Fibrogenesis
Pradere, J.-P., Troeger, J., Dapito, D., Mencin, A., & Schwabe, R. (2010) · Seminars in Liver Disease · doi:10.1055/s-0030-1255353 · Cited by 158 · see citing works
CD24-Siglec G/10 discriminates danger- from pathogen-associated molecular patterns
Liu, Y., Chen, G.-Y., & Zheng, P. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.09.006 · Cited by 147 · see citing works
DAMPs, ageing, and cancer: The ‘DAMP Hypothesis’
Huang, J., Xie, Y., Sun, X., Zeh, H. J., Kang, R., Lotze, M. T., & Tang, D. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2014.10.004 · Cited by 144 · see citing works
Site-Specific Blockade of RAGE-V<sub>d</sub>Prevents Amyloid-β Oligomer Neurotoxicity
Sturchler, E., Galichet, A., Weibel, M., Leclerc, E., & Heizmann, C. W. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4878-07.2008 · Cited by 136 · see citing works
Bianchi, M. E., & Manfredi, A. A. (2009) · Science · doi:10.1126/science.1172794 · Cited by 117 · see citing works
RAGE-Mediated Inflammation, Type 2 Diabetes, and Diabetic Vascular Complication
Yamamoto, Y., & Yamamoto, H. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00105 · Cited by 99 · see citing works
Julian, M. W., Shao, G., VanGundy, Z. C., Papenfuss, T. L., & Crouser, E. D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072354 · Cited by 85 · see citing works
Microparticles as a source of extracellular DNA
Pisetsky, D. S., Gauley, J., & Ullal, A. J. (2011) · Immunologic Research · doi:10.1007/s12026-010-8184-8 · Cited by 80 · see citing works
Cheng, M., Liu, H., Zhang, D., Liu, Y., Wang, C., Liu, F., & Chen, J. (2015) · American Journal of Nephrology · doi:10.1159/000381464 · Cited by 66 · see citing works
Receptor for advanced glycation endproducts and progressive kidney disease
Fukami, K., Taguchi, K., Yamagishi, S.-I., & Okuda, S. (2015) · Current Opinion in Nephrology and Hypertension · doi:10.1097/mnh.0000000000000091 · Cited by 46 · see citing works
Standardization of anti-DNA antibody assays
Pisetsky, D. S. (2013) · Immunologic Research · doi:10.1007/s12026-013-8415-x · Cited by 23 · see citing works
Host Response to Naturally Derived Biomaterials
Lopresti, S. T., & Brown, B. N. (2015) · Host Response to Biomaterials · doi:10.1016/b978-0-12-800196-7.00004-9 · Cited by 24 · see citing works
Kamiya, M., Kimura, N., Umezawa, N., Hasegawa, H., & Yasuda, S. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1191815 · Cited by 21 · see citing works
Motoyoshi, S., Yamamoto, Y., Munesue, S., Igawa, H., Harashima, A., Saito, H., Han, D., Watanabe, T., Sato, H., & Yamamoto, H. (2014) · Biochemical Journal · doi:10.1042/bj20140084 · Cited by 20 · see citing works
Emerging Roles of High-mobility Group Box-1 in Liver Disease
Wang, L., Dong, Z., Zhang, Y., & Peng, L. (2024) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2024.00317 · Cited by 8 · see citing works
- Authors
- Tian, J., Avalos, A. M., Mao, S.-Y., Chen, B., Senthil, K., Wu, H., Parroche, P., Drabic, S., Golenbock, D., Sirois, C., Hua, J., An, L. L., Audoly, L., La Rosa, G., Bierhaus, A., Naworth, P., Marshak-Rothstein, A., Crow, M. K., Fitzgerald, K. A., Latz, E., Kiener, P. A., & Coyle, A. J.
- Affiliations
- Boston University (US)
- University of Massachusetts Chan Medical School (US)
- Hospital for Special Surgery (US)
- Heidelberg University (DE)
- Corresponding author
- Coyle, Anthony J
- ORCID
- Venue
- Nature Immunology
- Published
- 2007-04-08
- Volume
- 8
- Issue
- 5
- Pages
- 487-496
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2130775443
- Cited by
- 1,372
- References
- 65
- Citations by year
- 2026: 28 · 2025: 33 · 2024: 41 · 2023: 42 · 2022: 56 · 2021: 59 · 2020: 60 · 2019: 65 · 2018: 70 · 2017: 68 · 2016: 85 · 2015: 86 · 2014: 74 · 2013: 94 · 2012: 83
- FWCI
- 39.84
- Type
- journal article
- Language
- en
- Update notices
- erratum (2007-07-01)
- Open access
- closed
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI0677497-01)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- TLR9, HMGB1, RAGE, CpG oligodeoxynucleotides, MyD88 signaling, plasmacytoid dendritic cells, B cells, cytokine production, systemic lupus erythematosus, autoimmune disease
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Antigen-Antibody Complex, B-Lymphocytes, Dendritic Cells, DNA-Binding Proteins, Lupus Erythematosus, Systemic, Mice, Inbred C57BL, Oligodeoxyribonucleotides, Receptors, Cell Surface, CpG Islands, HMGB1 Protein, Toll-Like Receptor 9, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
